Avastin could play an important role in improving the daily lives of patients with the most aggressive form of brain cancer

Analysis of BRAIN study shows that patients may have a
stabilisation or improvement in neurocognitive function and a
reduction in steroid use.

BASEL, Switzerland, Sept. 22, 2009--Roche (SIX: RO, ROG; OTCQX:
RHHBY) today announced that an analysis of the phase II BRAIN study
of Avastin (bevacizumab) alone or in combination with irinotecan
chemotherapy for the treatment of relapsed or progressive
glioblastoma (GBM) demonstrated that in addition to increasing the
chance of patients being alive without worsening of their disease
at six months (progression free survival; PFS-6*)1), Avastin-based
therapy may also lead to additional positive impact on
patients’ daily lives2). Adverse events in the BRAIN study
were consistent with those previously seen with Avastin and no new
safety signals were reported.

The analysis presented today at Europe’s largest
scientific meeting for cancer specialists, the joint 15th ECCO and
34th ESMO, showed that those patients who responded to
Avastin-based therapy may also have a stabilisation or improvement
in neurocognitive function and a reduction in their dose of
steroids2).

“Stabilising neurocognitive function and reducing reliance
on steroids can improve day to day life for patients with recurrent
GBM which, given the poor prognosis, is a key aim of
treatment,” said Professor James Vredenburgh, Medical
Director, Adult Clinical Service, Duke University Medical Center,
Durham, USA. “This analysis suggests that Avastin-based
therapy which has already demonstrated PFS benefits may also have a
positive impact on patients’ daily lives and should offer
hope to physicians, patients and their caregivers alike.”

Neurocognitive function includes the ability to think and
reason, to make judgements and remember things. A decline in this
function, a common consequence of GBM, can be distressing for both
patients and their families. Avastin based treatment was also
associated with lower use of steroids in some patients. Steroids
are an important part of managing symptoms in many patients with
GBM but they can lead to complications such as weight gain,
insomnia and behavioural changes. Reduction in steroid dose means
that physicians may be able to reduce the side effects of long term
steroid use.

GBM is the most common and the most aggressive type of primary
malignant brain tumour and most patients experience relapse or
progression of their disease following initial treatment3,4). When
the disease returns, prognosis is particularly poor and improving
day to day life for patients is a component of the treatment
aim.

“Avastin continues to demonstrate its benefits as a
treatment for an increasing variety of cancers,” said William
M. Burns, CEO of Roche’s Pharmaceuticals Division.
“Avastin based therapy has the potential to make a real
difference for patients with glioblastoma.”

Avastin precisely inhibits vascular endothelial growth factor
(VEGF) a key mediator of angiogenesis, the growth of new blood
vessels, which is essential for tumour growth and spread. GBM has
very high VEGF expression. By controlling angiogenesis, Avastin
controls tumour growth.

In May 2009, Avastin was granted accelerated approval for the
treatment of GBM patients with progressive disease following prior
therapy from the US Food and Drug Administration (FDA) based on
data from the BRAIN study (AVF3708g) which was recently published
in the Journal of Clinical Oncology1) and an NCI study (NCI
06-C-0064E). The data is currently being discussed with regulators
in Europe and has led to approvals in Switzerland, Albania,
Dominican Republic, India, Moldova and the Ukraine.

A large, over 900 patient phase III study of Avastin, for the
treatment of newly diagnosed GBM patients (AVAGLIO) is
underway.5)

About the BRAIN study
The BRAIN study was a US based open-label, multicentre,
non-comparative phase II study including 167 patients with
histologically confirmed GBM that had progressed following initial
treatment with temozolomide and radiation. The primary endpoints of
the BRAIN trial were progression free survival-6 (PFS-6), (defined
as the percentage of patients who remained alive and progression
free at 24 weeks) and objective response rate (ORR), (defined as a
complete or partial response on two consecutive MRIs obtained 4
weeks apart). Secondary endpoints explored included OS, PFS,
duration of response to treatment and safety. The BRAIN study
evaluated Avastin at a dose of 10mg/kg every two weeks, as a single
agent (BEV), or in combination with irinotecan chemotherapy
(BEV-IRI).

This latest analysis of the BRAIN study demonstrated that2):

Steroid use
Of the patients not requiring corticosteroids at baseline, more
than 75% Avastin and 65% Avastin plus chemotherapy patients did not
use corticosteriods post-baseline.

The majority of patients with an objective response or who were
alive and without progression at 24 weeks had sustained reduction
in steroid dose when receiving Avastin based therapy.
At baseline, over half of the patients (50.6% BEV and 52.4% BEV-IRI
pts) took systemic corticosteroids. Of these patients receiving
steroids at baseline:
In patients that responded (complete or partial) to Avastin-based
therapy, 57% and 64% of patients receiving Avastin and Avastin +
chemotherapy, respectively had a sustained reduction in steroid use
(defined as able to at least halve their steroid dose for at least
half the time they were on treatment )
In patients who were alive and without progression of disease at 24
weeks 58% and 86% demonstrated a sustained reduction in steroid
dose (defined as being able to at least halve steroid dose for at
least half the time on treatment) when receiving Avastin or Avastin
+ chemotherapy, respectively.
Neurocognitive function
The majority of patients with an objective response or alive and
without progression at 24 weeks** had improved or stable
neurocognitive function compared to baseline.

Of the patients with an objective response, 75% and 60.7% of
patients receiving Avastin and Avastin + chemotherapy, respectively
experienced stable or improved neurocognitive function at time of
their response relative to baseline
Of the patients with PFS greater than 6 months, 70.4% and 70% had
stable or improved neurocognitive function at week 24 relative to
baseline, when receiving Avastin or Avastin + chemotherapy,
respectively.
The BRAIN study previously demonstrated1):
When Avastin was evaluated as a single agent, the study showed that
at six months almost half (42.6%) of patients lived without their
disease advancing, as defined by progression-free survival (PFS).
When Avastin was combined with irinotecan, this figure increased to
50.3%.
In the study, nearly a third (28%) of patients responded to Avastin
as a single agent, meaning tumours decreased in size by at least
50%. When Avastin was combined with irinotecan, 38% of patients
responded to Avastin.
Patients receiving Avastin alone had a median overall survival of
9.2 months compared to 8.7 months for those receiving Avastin in
combination with irinotecan, which was a secondary endpoint in the
study. Most adverse events related to Avastin in this trial
appeared to be similar to those previously reported in other
Avastin studies1).
About Glioblastoma
Glioma (cancer of the glial cells) is the most common type of
malignant primary brain tumour (a tumour that originates in the
brain), accounting for approximately one third of all cases
diagnosed3). Glioblastoma (or glioblastoma multiforme; GBM) is the
most common and the most aggressive type of glioma3). The prognosis
for patients with GBM is poor, and generally depends on the success
of surgery to remove the tumour.

Glioblastoma affects approximately 13,000 people per year in the
EU3). Following initial treatment, glioblastoma tumours nearly
always return and currently, there are limited treatment options
for patients when these relapses occur4). According to historical
estimates, less than 10 percent of patients with recurrent GBM
respond to treatment and approximately 15 percent will live six
months without their disease getting worse1,5) . GBM is a
compelling therapeutic target for Avastin as these tumours have
among the highest levels of vascular endothelial growth factor
(VEGF) of any solid tumour.

About Avastin
Avastin is an antibody that specifically binds and blocks the
biological effects of VEGF (vascular endothelial growth factor).
VEGF is a key driver of tumour angiogenesis – an essential
process required for a tumour to grow and to spread (metastasize)
to other parts of the body. Avastin’s precise mode of action
allows it to be combined effectively with a broad range of
chemotherapies and other anti-cancer treatments. Avastin helps to
control tumour growth and extend survival with only a limited
impact on the side effects of chemotherapy.

Avastin has proven survival benefits across several types of
cancer. It is approved in Europe for the treatment of the advanced
stages of four common types of cancer: colorectal cancer, breast
cancer, non-small cell lung cancer (NSCLC) and kidney cancer. These
types of cancer collectively cause over 2.5 million deaths each
year6,7,8). In the US, Avastin was the first anti-angiogenesis
therapy approved by the FDA and it is now approved for the
treatment of five tumour types: colorectal cancer, non-small cell
lung cancer, breast cancer, brain (glioblastoma) and kidney (renal
cell carcinoma).

Over half a million patients have been treated with Avastin so
far. A comprehensive clinical programme with over 450 clinical
trials is investigating the use of Avastin in various tumour types
(including colorectal, breast, non-small cell lung, brain, gastric,
ovarian, prostate and others) and different settings (advanced or
early stage disease).

About Roche
Headquartered in Basel, Switzerland, Roche is a leader in
research-focused healthcare with combined strengths in
pharmaceuticals and diagnostics. Roche is the world’s largest
biotech company with truly differentiated medicines in oncology,
virology, inflammation, metabolism and CNS. Roche is also the world
leader in in-vitro diagnostics, tissue-based cancer diagnostics and
a pioneer in diabetes management. Roche’s personalised
healthcare strategy aims at providing medicines and diagnostic
tools that enable tangible improvements in the health, quality of
life and survival of patients.

In 2008, Roche had over 80’000 employees worldwide and
invested almost 9 billion Swiss francs in R&D.

The Group posted sales of 45.6 billion Swiss francs. Genentech,
United States, is a wholly owned member of the Roche Group. Roche
has a majority stake in Chugai Pharmaceutical, Japan. For more
information: www.roche.com.

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